Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction

Connie R Bezzina; Raha Pazoki; Abdennasser Bardai; Roos F Marsman; Jonas S S G de Jong; Marieke T Blom; Brendon P Scicluna; J Wouter Jukema; Navin R Bindraban; Peter Lichtner; Arne Pfeufer; Nanette H Bishopric; Dan M Roden; Thomas Meitinger; Sumeet S Chugh; Robert J Myerburg; Xavier Jouven; Stefan Kääb; Lukas R C Dekker; Hanno L Tan; Michael W T Tanck; Arthur A M Wilde

doi:10.1038/ng.623

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Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction

Journal article

Open access

Peer reviewed

Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction

Connie R Bezzina, Raha Pazoki, Abdennasser Bardai, Roos F Marsman, Jonas S S G de Jong, Marieke T Blom, Brendon P Scicluna, J Wouter Jukema, Navin R Bindraban, Peter Lichtner, …

Nature genetics, Vol.42(8), pp.688-U64

2010-08

DOI: https://doi.org/10.1038/ng.623

PMCID: PMC3966292

PMID: 20622880

Abstract

Acute Disease

Genome-Wide Association Study

Myocardial Infarction - mortality

Disease Susceptibility - complications

Humans

Middle Aged

Ventricular Fibrillation - mortality

Male

Death, Sudden, Cardiac - etiology

Anterior Wall Myocardial Infarction

Myocardial Infarction - complications

Netherlands

Ventricular Fibrillation - complications

Ventricular Fibrillation - physiopathology

Female

Myocardial Infarction - physiopathology

Aged

Arrhythmias, Cardiac - complications

Heart Arrest - complications

Odds Ratio

Sudden cardiac death from ventricular fibrillation during acute myocardial infarction is a leading cause of total and cardiovascular mortality. To our knowledge, we here report the first genome-wide association study for this trait, conducted in a set of 972 individuals with a first acute myocardial infarction, 515 of whom had ventricular fibrillation and 457 of whom did not, from the Arrhythmia Genetics in The Netherlands (AGNES) study. The most significant association to ventricular fibrillation was found at 21q21 (rs2824292, odds ratio = 1.78, 95% CI 1.47-2.13, P = 3.3 x 10(-10)). The association of rs2824292 with ventricular fibrillation was replicated in an independent case-control set consisting of 146 out-of-hospital cardiac arrest individuals with myocardial infarction complicated by ventricular fibrillation and 391 individuals who survived a myocardial infarction (controls) (odds ratio = 1.49, 95% CI 1.14-1.95, P = 0.004). The closest gene to this SNP is CXADR, which encodes a viral receptor previously implicated in myocarditis and dilated cardiomyopathy and which has recently been identified as a modulator of cardiac conduction. This locus has not previously been implicated in arrhythmia susceptibility.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.94 Cardiac Arrhythmia; 1.94.470 Brugada Syndrome
Web Of Science research areas: Genetics & Heredity
ESI research areas: Molecular Biology & Genetics

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Title: Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction
Creators: Connie R Bezzina - Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Raha Pazoki - Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Abdennasser Bardai - Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Roos F Marsman - Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Jonas S S G de Jong - Heart Failure Research Center, Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Marieke T Blom - Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Brendon P Scicluna - Heart Failure Research Center, Department of Experimental Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
J Wouter Jukema - Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands
Navin R Bindraban - Department of Social Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Peter Lichtner - Institute of Human Genetics, Klinikum Rechts der Isar Technische Universität München, Munich, Germany
Arne Pfeufer - Institute of Human Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany
Nanette H Bishopric - Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida, USA
Dan M Roden - Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Thomas Meitinger - Institute of Human Genetics, Helmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt, Neuherberg, Germany
Sumeet S Chugh - The Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
Robert J Myerburg - Division of Cardiology, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
Xavier Jouven - Université Paris Descartes, Assistance Publique-Hopitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France
Stefan Kääb - Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany
Lukas R C Dekker - Department of Cardiology, Catharina Hospital, Eindhoven, The Netherlands
Hanno L Tan - Heart Failure Research Center, Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Michael W T Tanck - Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Arthur A M Wilde - Heart Failure Research Center, Department of Cardiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
Publication Details: Nature genetics, Vol.42(8), pp.688-U64
Publisher: United States
Grant note: U19 HL065962 / NHLBI NIH HHS R01 HL071094 / NHLBI NIH HHS
Academic Unit: Miller School of Medicine; UMMG Dept of Medicine - Cardiovascular
Language: English
Resource Type: Journal article
PMID: 20622880
PMCID: PMC3966292
Record Identifier: 991031559580302976